Cross-reactive human B cell and T cell epitopes between influenza A and B viruses

Abstract

Influenza A and B viruses form different genera, which were originally distinguished by antigenic differences in their nucleoproteins and matrix 1 proteins. Cross-protection between these two genera has not been observed in animal experiments, which is consistent with the low homology in viral proteins common to both viruses except for one of three polymerase proteins, polymerase basic 1 (PB1). Recently, however, antibody and CD4+ T cell epitopes conserved between the two genera were identified in humans. A protective antibody epitope was located in the stalk region of the surface glycoprotein, hemagglutinin, and a CD4+ T cell epitope was located in the fusion peptide of the hemagglutinin. The fusion peptide was also found to contain antibody epitopes in humans and animals. A short stretch of well-conserved peptide was also identified in the other surface glycoprotein, neuraminidase, and antibodies binding to this peptide were generated by peptide immunization in rabbits. Although PB1, the only protein which has relatively high overall sequence homology between influenza A and B viruses, is not considered an immunodominant protein in the T cell responses to influenza A virus infection, amino acid sequence comparisons show that a considerable number of previously identified T cell epitopes in the PB1 of influenza A viruses are conserved in the PB1 of influenza B viruses. These data indicate that B and T cell cross-reactivity exists between influenza A and B viruses, which may have modulatory effects on the disease process and recovery. Although the antibody titers and the specific T cell frequencies induced by natural infection or standard vaccination may not be high enough to provide cross protection in humans, it might be possible to develop immunization strategies to induce these cross-reactive responses more efficiently.

Interval Between Infections and Viral Hierarchy Are Determinants of Viral Interference Following Influenza Virus Infection in a Ferret Model

“…Previous studies, in which infections with heterosubtypic influenza A viruses were separated by 8 weeks, showed a similar shortening of the duration of virus shedding [28]. Cross-reactive epitopes between influenza A and B viruses have been reported in the fusion peptide of hemagglutinin (HA) and the enzymatic region of neuraminidase [30]. Generation of cross-reactive T cells has yet to be investigated, but we observed no protection, or change in kinetics, when ferrets were infected with influenza A virus and then challenged with influenza B virus 8 weeks later, and vice versa (data not shown).…”

“…In this study, we used the ferret model of human influenza to investigate viral interference and its effect on the probability and kinetics of subsequent infection. We assessed the potential for viral interference between antigenically unrelated influenza virus types (A and B), for which few T and B lymphocyte epitopes are similar [30], and between influenza virus subtypes that share T and B lymphocyte epitopes (A[H3N2] and A[H1N1]pdm09 viruses). Of direct relevance to recent epidemiological reports, combinations of influenza viruses that circulated in 2009 and 2010 were assessed.…”

A plant-derived quadrivalent virus like particle influenza vaccine induces cross-reactive antibody and T cell response in healthy adults

“…Although most of the work on CMI to date has focused on the conserved epitopes of internal influenza proteins like nucleoprotein (NP) and M protein, recent data demonstrate that the influenza HA molecule also contains class I-and class II-restricted epitopes and that HA-specific T cell responses can be detected after influenza infection or vaccination [16][17][18][19][20].…”

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“…In this regard, there is an urgent need for the development of an effective universal influenza vaccine that provides a long-lasting broad cross-protective immunity and is able to protect against the influenza A and B viruses of all known subtypes. Several examples of the crossreactive antibodies that neutralize the HA of groups I and II of influenza viruses A as well as the antibodies that react with A and B viruses are known to date [21]. These results indicate that the creation of the universal influenza vaccine is possible.…”